This revised application seeks support to establish a Comprehensive NeuroAIDS Core Center (CNACC) at the Temple University School of Medicine in order to bring highly needed infrastructure for basic scientists and clinicians involved in HIV-1/AIDS research and neurological, neurodegenerative, and neurobehavioral disorders. The central theme of CNACC is structured based on our hypothesis that understanding the mechanisms of HIV-1/CNS interactions at the molecular, cellular, and experimental animal model levels and bidirectional communication of laboratory findings and clinical observations to validate basic science discoveries are prerequisites for the development of effective, safe, and reliable approaches for early diagnostics and therapeutics for AIDS-associated neurological dysfunctions. The CNACC will provide unprecedented infrastructure to a large group of neuroAIDS investigators who plan to pursue their objectives using multidisciplinary approaches in cell culture, small animal models, and in the clinical setting for assessing gene expression and biomarker identification at the cellular and molecular levels. Further, through the Developmental Core, the CNACC will provide a unique opportunity for training and mentoring of junior and clinical investigators and attract and develop physician scientists in the field of neuroAIDS. Through CNACC, we will provide start-up funds for new and innovative pilot projects of newly recruited, independent investigators and will support feasibility studies for more established neuroAIDS investigators. The funding through this center will create a unique infrastructure that will serve to enhance and extend the effectiveness of ongoing HIV-1 investigations and promote translational research in neuroAIDS at Temple and other medical institutions in the greater Philadelphia area that are involved in basic science and clinical AIDS research. With its comprehensive structural organization encompassing broadly based cores ranging from molecular biology to experimental animals to the clinical arena directed by skilled and highly competent investigators from various disciplines, CNACC will support research in a variety of areas such as virology, basic and behavioral neuroscience, and clinical science, all of which are aimed toward the discovery of better diagnostics and effective therapeutic agents toward AIDS/CNS disorders.